title: Dendritic cell-directed lentivector vaccine induces antigen-specific immune responses against murine melanoma.
abstract: Lentivectors are potential vaccine delivery vehicles because they can efficiently transduce a variety of non-dividing cells, including antigen-presenting cells, and do not cause expression of extra viral proteins. To improve safety while retaining efficiency, a dendritic cell (DC)-specific lentivector was constructed by pseudotyping the vector with an engineered viral glycoprotein derived from Sindbis virus. We assessed the level of anti-tumor immunity conferred by this engineered lentivector encoding the melanoma antigen gp100 in a mouse model. Footpad injection of the engineered lentivectors results in the best antigen-specific immune response as compared with subcutaneous and intraperitoneal injections. A single prime vaccination of the engineered lentivectors can elicit a high frequency (up to 10%) of gp100-specific CD8(+) T cells in peripheral blood 3 weeks after the vaccination and this response will be maintained at around 5% for up to 8 weeks. We found that these engineered lentivectors elicited relatively low levels of anti-vector neutralizing antibody responses. Importantly, direct injection of this engineered lentivector inhibited the growth of aggressive B16 murine melanoma. These data suggest that DC-specific lentivectors can be a novel and alternative vaccine carrier with the potential to deliver effective anti-tumor immunity for cancer immunotherapy.
authors.affiliation: Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: H G
authors.initials: HG
authors.lastname: Yang
authors.forename: B L
authors.initials: BL
authors.lastname: Hu
authors.forename: L
authors.initials: L
authors.lastname: Xiao
authors.forename: P
authors.initials: P
authors.lastname: Wang
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D017931:DNA Primers / Q000235:genetics; D003713:Dendritic Cells / Q000378:metabolism* / Q000821:virology; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D005434:Flow Cytometry; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods*; D016086:Lentivirus; D008545:Melanoma / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests
chemical_list: D019496:Cancer Vaccines; D016207:Cytokines; D017931:DNA Primers